JP5448888B2 - Liquid mixing device - Google Patents

Description

  The present invention relates to a liquid mixing apparatus applicable to a small chemical analysis / synthesis system or the like that performs chemical analysis or chemical synthesis on a chip, and more specifically to a liquid mixing apparatus using induced charge electroosmosis.

  A micropump using electroosmosis is used in fields such as μTAS (Micro-Total Analysis System) because of its relatively simple structure and easy mounting in a microchannel (microchannel). Yes.

  Under these circumstances, in recent years, micropumps using induced-charge electroosmosis (ICEO) can increase the flow rate of liquid and suppress the chemical reaction that occurs between the electrode and liquid by AC drive. It is attracting attention for reasons such as being able to.

  Patent Document 1 and Non-Patent Document 1 disclose a mixer (mixing device) using induced charge electroosmosis, which utilizes a vortex generated by an ICEO flow around a cylindrical metal post.

  Non-Patent Document 2 discloses a mixer in which a vertical electric field and an oblique electric field are alternately applied to a cylindrical metal post to alternately switch two vortices.

U.S. Pat. No. 7,081,189

M.M. Z. Bazant and T.W. M.M. Squires, Phys. Rev. Lett. 92,066101 (2004) H. Zhao and H.C. Bau, Phys. Rev. E 75 066217 (2007)

  In a microchannel, since the Reynolds number is low, mixing by turbulent flow cannot be expected, and mixing is mainly by molecular diffusion.

  Therefore, in the case where the vortex caused by the ICEO flow disclosed in Patent Document 1 and Non-Patent Document 1 is generated in the microchannel, the time required to obtain sufficient mixing and the necessary channel length are relatively long. The problem of lengthening arises.

  On the other hand, since the mixer described in Non-Patent Document 2 requires an oblique electric field inclined in an oblique direction with respect to the flow path wall surface, when an apparatus is actually configured, a certain device is required for electrode arrangement. There is a risk that miniaturization will be difficult.

  An object of the present invention is to provide a liquid mixing apparatus capable of efficiently mixing liquids in a short time and capable of being miniaturized.

A liquid mixing apparatus provided by the present invention includes a micro flow channel for transporting a liquid, a conductive member provided in the flow channel, and an electrode for applying an electric field to the conductive member. Eddy current generating means for generating a vortex flow of the liquid in the flow path, directional flow generating means for generating the flow of the liquid in a direction along the flow path, and the vortex flow and the directional flow at a predetermined frequency. And switching means for switching alternately .

  The liquid mixing apparatus of the present invention includes a vortex generating means for generating a vortex of liquid in the flow path, a directional flow generating means connected to the end of the flow path to generate a flow in the direction along the flow path, and these It has means switching means, and it is possible to switch between vortex flow and directional flow. This enables efficient liquid mixing in a short time. Furthermore, it is possible to provide a liquid mixing device that does not require an oblique electric field and is easy to be miniaturized and integrated.

(A) is a schematic diagram showing an example of the liquid mixing apparatus of the present invention, (b) is a timing chart showing an example of timing of drive switching by the switching means. The figure which shows the flow velocity distribution of the liquid in the liquid mixing apparatus of this invention The figure which shows the position of the liquid in the liquid mixing apparatus of this invention in a certain time The figure which shows the position of the liquid in the liquid mixing apparatus of this invention in a certain time The figure which shows the position of the liquid in the liquid mixing apparatus of this invention in a certain time The figure which shows the position of the liquid in the liquid mixing apparatus of this invention in a certain time Graph showing the relationship between mixing coefficient and Strouhal number Graph showing the relationship between mixing time and Strouhal number Graph showing the relationship between mixing time and Strouhal number Schematic diagram showing an example of the liquid mixing apparatus of the present invention The figure which shows the position of the liquid in the liquid mixing apparatus in a comparative example Diagram showing the position of the liquid in the liquid mixing device Schematic diagram showing an example of the liquid mixing apparatus of the present invention

  Hereinafter, the liquid mixing apparatus of the present invention will be described with reference to the drawings.

  A liquid mixing apparatus according to the present invention includes a flow path for transporting a liquid, a conductive member provided in the flow path, and an electrode for applying an electric field to the conductive member. Eddy current generating means for generating the liquid vortex flow, directional flow generating means for generating the liquid flow in the direction along the flow path, and switching means for switching between the vortex flow and the directional flow. It is characterized by having.

  FIG. 1 is a schematic view showing an example of the liquid mixing apparatus of the present invention.

  In FIG. 1, 5 is a flow path (length L, width w, depth d2 (> w)) for transporting liquid, 3 is a conductive member provided in the flow path, 4 is electrodes 1 and 2 Is a power source that applies an electric field to the conductive member 3. Here, the electrodes 1, 2, the power source 4, and the conductive member 3 constitute eddy current generating means for generating a liquid vortex in the flow path.

  8a and 8b are pumps as directional flow generating means for generating a liquid flow in the direction along the flow path (the direction in which the flow path extends) in the flow path 5. By operating this pump, A pressure difference ΔP is generated in the liquid at the inlet and outlet. Reference numeral 9 denotes switching means for switching between the eddy current generating means and the directional flow generating means.

  In the apparatus of FIG. 1, an electric field is generated by applying a voltage between the electrodes 1 and 2, and an electric charge is induced on the surface of the conductive member 3 by this electric field. Charged components (cations, negative ions, etc.) in the liquid are attracted to the induced charges, and so-called electric double layers are formed. An eddy current is generated due to the electroosmotic flow that occurs in the electric double layer portion formed in a pair with the induced charge.

  In the liquid mixing apparatus of the present invention, the liquid can be efficiently mixed in a short time by switching between the vortex flow and the directional flow as the liquid flow mainly generated in the flow path.

  As a material constituting the conductive member, a material that induces an electric charge by an electric field is used, and in addition to a metal (for example, gold or platinum), carbon or a carbon-based material may be used. However, this member is also preferably made of a material that is stable with respect to the liquid to be conveyed.

  The number of conductive members provided in the flow path is preferably plural in order to efficiently generate a vortex, and the length of the flow path, the size of the conductive member, the viscosity of the liquid to be transported, etc. Can be selected.

  The conductive member is preferably arranged in a zigzag shape with respect to the direction in which the liquid is conveyed with the center of the flow path as a boundary from the viewpoint of the efficiency of vortex flow. In FIG. 1, a total of four are arranged, two at the center of the flow path, but the number can be selected as appropriate.

  In FIG. 1, the electrodes for applying an electric field to the conductive member are provided with a pair of opposing electrodes 1 and 2, but three or four or more electrodes are provided as long as the charge can be effectively induced in the conductive member. Can also be arranged. Examples of the material constituting the electrode include gold, platinum, carbon, carbon-based conductors, and the like in addition to general electrode materials made of metal or the like. Although FIG. 1 shows an example in which an AC (alternating current) power source is used as a power source for generating eddy currents and is driven using an electric field, a DC (direct current) power source can also be used.

  In the present invention, various pumps can be used as the directional flow generating means for generating a flow in the direction along the flow path, but a diaphragm generally used in the field of μTAS (micro total analysis system) and the like. It is preferable to use a micro pump such as a pump, a piezoelectric actuator pump, an electrophoretic pump, or an electroosmotic pump.

  The switching means between the directional flow generating means (pump) and the vortex flow generating means can be configured using, for example, an arbitrary waveform generator having two channels.

  This generator generates, for example, a rectangular wave (gate pulse) having a maximum value of 5V (ON state) and a minimum value of 0V (OFF state) in opposite phases in channel 1 and channel 2, and directivity The flow generating means has an interface that is controlled to be ON or OFF according to the channel 1 gate pulse, and the vortex generating means is controlled to be ON or OFF according to the channel 2 gate pulse. You will have an interface that will be

Of course, the AC voltage may be directly connected to the electrode by appropriately adjusting the peak drive voltage (+ V ₀ , −V ₀ ) and frequency during the ON state period of the channel 2. Moreover, it is also possible to integrate the electric circuit part included in the switching means from the viewpoint of configuring a small system on the IC chip.

In the present invention, the flow path for conveying the fluid can be made of a material generally used in the field such as μTAS. Specifically, it can be composed of a material that is stable with respect to the liquid to be transported, and examples of such a material include SiO ₂ , Si, a fluororesin, and a polymer resin.

  The size of the channel is preferably set to a size that can be used as a so-called microreactor. The specific channel width is preferably 1000 μm or less, more preferably 500 μm or less, and desirably 200 μm or less. As the channel width becomes narrower, the liquid diffusion distance becomes shorter, leading to a reduction in mixing time and reaction time. The depth of the channel is preferably deeper (larger) than the channel width from the viewpoint of increasing the contact area between the liquids to be mixed. Specifically, the depth / flow path width is 0.1 or more, more preferably 0.5 or more, more preferably 1 or more, optimally 2 or more. Furthermore, increasing the depth / flow path width also has the effect of increasing the cross-sectional area of the flow path and allowing more fluid to flow.

  In the present invention, the liquid that can be transported in the flow path basically includes polar molecules containing a charged component, and examples thereof include water and solutions containing various electrolytes.

  Hereinafter, the present invention will be described in detail with specific examples.

FIG. 1 is a cross-sectional view showing the mixing apparatus of the first embodiment. In the figure, 1 and 2 are a pair of electrodes, 3 is a conductive member, 4 is a power source, 5 is a channel having a width w (= 100 μm), a length L (= 225 μm), and a depth d ₂ (> w). The flow path 5 is filled with a polarizable solution such as water or an aqueous electrolyte solution. Here, the pair of electrodes 1 and 2 are means for applying a DC or AC electric field to the flow path. The electrodes 1 and 2, the power source 4, and the conductive member 3 constitute eddy current generating means for generating a liquid vortex in the flow path.

  Reference numerals 8a and 8b denote pumps as directional flow generating means that are connected to the end of the flow path 5 and generate a flow in a direction along the flow path.

  Reference numeral 9 denotes switching means for alternately switching between the directional flow generated by the directional flow generation means 8a and 8b and the vortex flow generated by the vortex flow generation means.

  The present invention can provide a high-performance liquid mixing apparatus (micromixer) that can shorten the flow path length and time required for mixing by switching between the two types of flows, and can be easily miniaturized and integrated without an oblique electric field.

  Here, the eddy current generating means includes a conductive member 3 disposed in the flow path 5 and electrodes 1 and 2 for applying an electric field to the conductive member 3, and a pair of charges induced in the conductive structure 3 by the electric field. The electroosmotic flow (ICEO) occurring in the electric double layer portion formed by forming Since the vortex flow generated by the ICEO flow is used, the flow velocity of the vortex flow can be increased, and the AC drive can be effective in avoiding the decomposition of a compound that causes a problem in the case of DC.

In this embodiment, the conductive member 3 is formed of a cylinder having a radius c (diameter 2c). In FIG. 1, φ is a parameter representing a position on a cylinder, and E represents a vertical electric field perpendicular to the electrode. The positions of the four cylinders are indicated by (x _i , y _i ) (i = 1, 2, 3, 4), and 2δ (= d ₀ ) indicates the interval in the x direction of the cylinder arrangement.

That is, the x position of the cylinder at the lower part of the flow path is x ₁ = x ₃ = 0.5 w + δ, and the x position of the cylinder at the upper part of the flow path is x ₂ = x ₄ = 0.5 w−δ, y ₁ / w = 0. .45, y ₂ /w=0.9, y ₃ /w=1.35, y ₄ /w=1.8.

FIG. 1B is a time chart for switching between driving by the directional flow generating means and driving by the vortex generating means, and T ₁ indicates a pressure difference (inlet of the flow path) by the directional flow generating means. And the pressure difference at the outlet). Further, T ₂ is the AC voltage application period by vortex generating means. T = T ₁ + T ₂ indicates a switching cycle.

  FIG. 2 is a calculation diagram of the flow velocity distribution of the apparatus of the present embodiment, FIG. 2A is a flow velocity distribution diagram of the directional flow generated by the directional flow generating means 8a and 8b, and FIG. It is a flow velocity distribution map of the vortex generated by the vortex generator.

The calculated value here is based on the calculation using the Stokes fluid equation considering the induced charge penetration effect.
c / w = 0.1, δ / w = 0.3, pressure difference ΔP = 2.4 Pa (pressure gradient ΔP / L) between the inlet and outlet of the flow path by the directional flow generating means, w = 100 μm, L / Calculation is made assuming that w = 2.25 and the applied voltage V ₀ = 2.38 V of the eddy current generating means.

  3, 4, 5, and 6 are diagrams illustrating the position of the liquid in the liquid mixing apparatus calculated using the periodic boundaries. The two types of liquids that flow Lq1 and Lq2 in FIG. 1 into the inlet of the flow path 5 are shown as 31 and 32 in FIG. 3 (t = 0), and the positional changes of these two types of liquid over time are shown in FIG. (T = 100 ms), FIG. 5 (t = 200 ms), and FIG. 6 (t = 500 ms). It can be understood from FIG. 6 that the two liquids are well mixed in a time of about 500 ms. Here, the directional flow generation period and the vortex generation period were set to T / 2 = 20 ms.

FIG. 7 shows the Strouhal number St of the mixing coefficient (ε _{3, max} ) representing the degree of mixing of the liquid after a sufficient time defined by the box measurement method, which is a method for quantitatively evaluating the mixing. ₁ = the _{fd 1 / U 1, St 0} = fd 0 / U 0 shows the dependency graph (calculated view).

Here, the Strouhal number is a dimensionless number of inertial force due to time change and inertial force due to location movement, f is the switching frequency, d ₁ is the width of the vortex in the direction along the flow path, and d ₀ is the vortex flow. The width in a direction perpendicular to the direction along the flow path, U ₁ represents the average flow velocity of the liquid in the direction along the flow path, and U ₀ represents the velocity of the vortex in the vertical direction.

  The mixing factor is

で定義される。

Defined by

However, if n _i <n _ave ω _i = n _i / n _ave , otherwise ω _i = 1. In addition, n _ave = N ₃ / K, N ₃ = (N ₁ N ₂ ) ^0.5 , n _i = (n ₁ n ₂ ) ^0.5 , and n ₁ and n ₂ are the virtual particles 1 and 2. The number in the box, N ₁ = N ₂ = 20 × 40 = 800 is the total number of virtual fluid particles 1 and 2, and K = 10 × 20 = 200 indicates the number of evaluation boxes.

Here, ω _i = n _i / n _ave becomes a low value in a box having an average number of particles or less, becomes 1 in a box having an excess particle number that is more than the average number of particles, and is considered to be well mixed (ε ₃ is 1). The better the mixing is, the better the mixing is. Therefore, as the virtual particles of the two kinds of liquids 31 and 32 spread uniformly throughout the entire flow path, the mixing coefficient approaches 1 and shows a well-mixed state as a whole.

It can be seen from FIG. 7 that good mixing is obtained with St ₁ = fd ₁ / U ₁ <1 and St ₀ = fd ₀ / U ₀ <1.

8 shows the relationship between the mixing time t _m and the Strouhal number, and FIG. 9 shows the relationship between the mixing distance L _m and the Strouhal number.

8 and 9, from the condition that St ₁ = fd ₁ / U ₁ <1, St ₀ = fd ₀ / U ₀ <1, t _m is about 1 s, L _m is about 1 mm, and a short time. It can be seen that sufficient mixing occurs at the distance. However, T ₀ = 1 ms. The solid line, the broken line, and the dotted line are analytical solutions based on a simple model when the switching time is T / (2T ₀ ) = 20, 40, 80. Further, the mixing distance is a distance required in an actual flow path that does not use a periodic condition as shown in FIG. 3, and is L _m = U ₁ t _m .

  Usually, it is said that a mixing time of about 60 s or more and a mixing channel length of about 1 cm are required in a channel having a channel width of about 100 μm, so that the present invention can greatly reduce the mixing time and the mixing channel length. . In the calculation, we considered the limit where the Reynolds number is zero and the Piclay number is infinite. Here, the Piclay number is a dimensionless number related to the diffusion coefficient, and the diffusion coefficient is 0 when the Piclay number is infinite.

  In the present invention, since chaotic mixing for switching plural kinds of flows is used, it can be seen that the present invention is effective even when the Reynolds number is extremely low and the Piclay number is large.

  In addition, the liquid mixing apparatus of the present invention is extremely useful in a microfluidic system that has a low Reynolds number and cannot be expected to be mixed by turbulent flow. The liquid mixing apparatus of the present invention can be applied to various fields to which a microfluidic system can be applied. Specifically, DNA and protein analysis, cell sorting, high-throughput screening, chemical reaction, minute amount (1 It can be used for a moving means of −100 nl).

  Since the molecular weight is large in DNA, protein, or cells, the diffusion coefficient is small, and the number of Piclays in the system is extremely large. Therefore, the mixing apparatus of the present invention that is effective even when the number of Piclays is infinite is extremely useful. Become. Furthermore, since a microfluidic device used for chemical analysis or the like is usually not expensive so as to be disposable and has a simple structure, the present invention can also be a suitable mixing apparatus in this respect.

(Comparative Example 1)
FIG. 11 and FIG. 12 are diagrams showing the position of the liquid in the liquid mixing apparatus when the vortex flow and the directional flow are generated simultaneously without switching.

  In these figures, the two kinds of liquids to be mixed are shown as 801 and 802, and the positional changes over time are shown in FIG. 11 (a) (t = 0 ms), FIG. 11 (b) (t = 100 ms), and FIG. a) (t = 200 ms) and FIG. 12B (t = 500 ms).

  From these figures, it can be understood that the device of this example without switching does not achieve good mixing over time, unlike the device shown in Example 1.

  That is, when the molecular diffusion is extremely small, good mixing does not occur unless the vortex flow and the directional flow are switched.

  FIG. 9 is a diagram showing the characteristics of the liquid mixing apparatus according to the second embodiment of the present invention. The apparatus of the present embodiment is characterized by having directional flow generating means 61a and 61b instead of the directional flow generating means 8a and 8b (pump) shown in the first embodiment.

  The directional flow generating means 61a and 61b, in the positions sandwiching the elliptical conductive members 13a and 13b, respectively, generate a flow in the reverse direction among the liquid flows generated by applying an electric field to the conductive members. The suppression members 65a and 65b to be suppressed are arranged.

  Reference numeral 62 denotes eddy current generating means similar to that shown in the first embodiment.

  In the apparatus of the present embodiment, a power source connected to the vortex generator 62 and a power source connected to the directional flow generators 61a and 61b are connected to the switching unit 9 to control the flow of liquid. .

  In this apparatus, the fluid flow from the left side to the right side in FIG. 9 is assumed to be the forward direction, the forward flow by the directional flow generator 61a, the vortex flow by the vortex generator 62, the reverse flow by the directional flow generator 61b, and the vortex It is possible to sequentially generate a liquid flow in the order of the vortex flow by the generating means 62 (alternate switching).

  In the apparatus of this embodiment that performs such switching, the substantial flow path length can be greatly reduced to about 3L = 6.75 μm.

1 Electrode 3 13a 13b Conductive member 8a 8b 61a 61b Directional flow generating means 62 Eddy current generating means 9 Switching means

Claims (5)

A micro flow path for transporting a liquid, a conductive member provided in the flow path, and an electrode for applying an electric field to the conductive member, and the electric field generates a vortex flow of the liquid in the flow path Eddy current generating means, directional flow generating means for generating the liquid flow in the direction along the flow path, and switching means for alternately switching the vortex flow and the directional flow at a predetermined frequency. A liquid mixing apparatus. The liquid mixing apparatus according to claim 1, wherein a flow path width of the micro flow path is 1000 μm or less.   3. The liquid mixing apparatus according to claim 1, wherein the eddy current generating unit uses an electroosmotic flow caused by an electric double layer generated in the conductive member by the electric field. Liquid according to any one of claims 1乃optimum 3, characterized in that the switching means for switching the direction of flow of the liquid caused due to the directional flow generating means to the directional flow generating means is connected Mixing equipment. A micro flow path for transporting a liquid, a conductive member provided in the flow path, and an electrode for applying an electric field to the conductive member, and the electric field generates a vortex flow of the liquid in the flow path Eddy current generating means, directional flow generating means for generating the liquid flow in the direction along the flow path, and switching means for switching between the vortex flow and the directional flow,
Switching means for switching the flow direction of the liquid generated due to the directional flow generation means is connected to the directional flow generation means, and the first flow of the liquid is introduced into the flow path using the switching means. direction direction flow, vortex of the liquid, the second direction of the directional flow, liquids mixing apparatus you characterized by sequentially generating vortices of the liquid in the liquid.

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